Synthesis of acetonides from aryl silanes

ABSTRACT

The present invention is related to cis-diols and biological methods of producing cis-diols. The present invention further relates to processes for subsequently converting such silane cis-diols to the more stable acetonide derivatives, as well as a process for converting silane cis-diols to the corresponding catechols and the compounds produced thereby. The present invention also provides chemical methods for the conversion of said silane cis-diols and acetonide compounds to epoxy, saturated and otherwise modified derivatives. It is emphasized that this abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that is will not be used to interpret or limit the scope or meaning of the claims. 37 CFR 1.72(b).

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.10/453,468, filed Jun. 3, 2003, which claims priority to U.S.Provisional Application No. 60/385,373 filed Jun. 3, 2002 and U.S.Provisional Application No. 60/435,187 filed Dec. 18, 2002.

BACKGROUND OF THE INVENTION

The present invention relates to dioxygenation of aryl silanes and, moreparticularly, to processes for converting aryl silanes to a new class ofchiral cis-diols by contact with a chemical or biological catalyst suchas dioxygenase-producing bacteria in the presence of molecular oxygen(O₂) and the chiral cis-diols produced thereby. The present inventionfurther relates to a process for subsequently converting such silanecis-diols to the more stable acetonide derivatives, as well as a processfor converting silane cis-diols to the corresponding catechols bytreatment with diol dehydrogenase enzyme and the compounds producedthereby. The present invention also provides chemical methods for theconversion of said silane cis-diols and acetonide compounds to epoxy,saturated and otherwise modified derivatives. The chiral intermediatesproduced by the process of the instant invention represent a novel classof compounds having potential value in the synthesis of fine chemicals,including pharmaceuticals. It is also contemplated that the chiralsilicon materials of the present invention may find application inenantioselective separations and optical applications.

The enzymatic dioxygenation of substituted aromatics to cis-diols isknown in the art as a means for synthesizing certain chiral moleculesfrom achiral precursors. Several enzymes are known to affect thistransformation, including toluene dioxygenase (EC 1.14.12.11),naphthalene dioxygenase (EC 1.14.12.12), and other aromatic oxygenases,which act on or catalyze a wide range of substrates. The followingdiagram illustrates this catalytic reaction:

Although the biotransformation of non silicon-containing substitutedaromatics to cis-diols by enzymatic dioxygenation is known (e.g.,Hudlicky T. et al., (1999) Enzymatic dihydroxylation of aromatics inenantioselective synthesis: expanding asymmetric methodology,Aldrichimica Acta, Vol. 32, No. 2, pp. 35-62), there is a need forprocesses that convert aryl silanes to chiral cis-diols or catechols andfor such chiral cis-diols or catechols.

SUMMARY OF THE INVENTION

In accordance with one aspect of the present invention, a method forconverting an aryl silane to a corresponding cis-diol is provided. Themethod comprises providing an aryl silane substrate, wherein the arylsilane has at least one aromatic component and at least one siliconatom, and contacting a dioxygenase enzyme with the aryl silane substratesuch that said aryl silane substrate is converted to a correspondingcis-diol. The method may further comprise reacting the cis-diol with2,2-dimethoxypropane to convert the cis-diol to an acetonide derivative.The method may further comprises contacting a diol dehydrogenase enzymewith the cis-diol to convert the cis-diol to a corresponding catechol.

In accordance with another aspect of the present invention, a compoundcomprising a cis-diol is provided. The cis-diol has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, an aryl, a linear or branched C₁-C₁₈ alkyl, a linear orbranched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, OR, SR,NR₂₋₃, or O(CO)R; and R is hydrogen, linear or branched C₁-C₁₈ alkyl, orSiR¹R²R³.

In accordance with yet another aspect of the present invention, acompound comprising a cis-diol is provided. The compound has theformula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is a divalent linear or branched C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, or C₂-C₁₈ alkynyl spacer, except when X═C₂ alkynyl andR¹═R²═R³ then R¹═R²═R³ cannot be —CH₃.

In accordance with a further aspect of the present invention, a compoundcomprising a silane cis-diol is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-5; and R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³.

In accordance with the present invention, a compound comprising a silanecis-diol is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-5; and R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³.

In accordance with a further aspect of the present invention, a compoundcomprising a silane cis-diol is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is a divalent linear or branched C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl spacer, S, O or NR₁₋₂.

In accordance with another aspect of the present invention, a compoundcomprising an acetonide is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, an aryl, a linear or branched C₁-C₁₈ alkyl, a linear orbranched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, OR, SR,NR₂₋₃, or O(CO)R, except when R¹═R²═R³ then R¹═R²═R³ cannot be —CH₃; andR is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³.

In accordance with yet another aspect of the present invention, acompound comprising an acetonide is provided. The compound has theformula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is a divalent linear or branched C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, or C₂-C₁₈ alkynyl spacer, except when X═C₂ alkynyl andR¹═R²═R³ then R¹═R²═R³ cannot be —CH₃.

In accordance with a further aspect of the present invention, a compoundcomprising an acetonide is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-5; and R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³.

In accordance with another aspect of the present invention, a compoundcomprising an acetonide is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-5; and R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³.

In accordance with yet another aspect of the present invention, acompound comprising an acetonide is provided. The compound has theformula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is a divalent linear or branched C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl spacer, S, O or NR₁₋₂.

In accordance with a further aspect of the present invention, a compoundcomprising a catechol is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, an aryl, a linear or branched C₁-C₁₈ alkyl, a linear orbranched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, OR, SR,NR₂₋₃, or O(CO)R; and R is hydrogen, linear or branched C₁-C₁₈ alkyl, orSiR¹R²R³.

In accordance with another aspect of the present invention, a compoundcomprising a catechol is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is a divalent linear or branched C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, or C₂-C₁₈ alkynyl spacer.

In accordance with a further aspect of the present invention, a compoundcomprising a catechol is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-5; and R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³.

In accordance with another aspect of the present invention, a compoundcomprising a catechol is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is-0-5; and R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³.

In accordance with yet another aspect of the present invention, acompound comprising a catechol is provided. The compound has theformula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is a divalent linear or branched C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl spacer, S, O or NR₁₋₂.

In accordance with another aspect of the present invention, a compoundis provided. The compound comprises:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer, except thatwhen X=nothing then R¹, R², and R³ cannot be R¹═R²═CH₃ and R³═H orR¹═R²═R³═CH₃.

In accordance with another aspect of the present invention, a di-O-acylis provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R⁵ is linear or branched C₁-C₁₈ alkyl,halomethyl, linear or branched C₂-C₁₈ alkenyl, or linear or branchedC₂-C₁₈ alkynyl; R is hydrogen, linear or branched C₁-C₁₈ alkyl, orSiR¹R²R³; and X is nothing, a divalent linear or branched C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer.

In accordance with a further aspect of the present invention, a silylether is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, or C₂-C₁₈ alkynyl spacer.

In accordance with another aspect of the present invention, a boronateester is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R⁵ is aryl, linear or branched C₁-C₁₈ alkyl,linear or branched C₂-C₁₈ alkenyl, or linear or branched C₂-C₁₈ alkynyl;R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and X isnothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, andC₂-C₁₈ alkynyl spacer.

In accordance with another aspect of the present invention, an epoxy isprovided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer.

In accordance with a further aspect of the present invention, an epoxyis provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ -alkyl, C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer, except whenX=nothing then R¹, R², and R³ cannot be R¹═R²═R³═CH₃.

In accordance with another aspect of the present invention, a partiallyor fully saturated compound is provided. The compound has the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer.

In accordance with yet another aspect of the present invention, apartially or fully saturated compound is provided. The compound has theformula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer.

In accordance with another aspect of the present invention, a silanol isprovided. The compound has the formula:

wherein: R¹ and R² are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer.

In accordance with yet another aspect of the present invention, asilanol is provided. The compound has the formula:

wherein: R¹ and R² are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈alkyl, or SiR¹R²R³; and X is nothing, a divalent linear or branchedC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, and C₂-C₁₈ alkynyl spacer.

In accordance with a further aspect of the present invention, an alkoxycompound is provided. The compound comprises:

wherein: R¹ and R² are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; R⁵ is an aryl, a linear or branched C₁-C₁₈ alkyl, alinear or branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl;n is 0-3; R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³;and X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈alkenyl, and C₂-C₁₈ alkynyl spacer.

In accordance with another aspect of the present invention, an alkoxycompound is provided. The compound comprises:

wherein: R¹ and R² are each independently selected from hydrogen, ahalogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branchedC₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR,NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear orbranched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear orbranched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃,O(CO)R, SiR¹R²R³, or a bridging group between two arene or substitutedarene moieties; R⁵ is an aryl, a linear or branched C₁-C₁₈ alkyl, alinear or branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl;n is 0-3; R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³;and X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈alkenyl, and C₂-C₁₈ alkynyl spacer.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

For purposes of defining and describing embodiments of the presentinvention, the following terms will be understood as being accorded thedefinitions presented hereinafter.

As used herein, the term “independently” or the equivalents thereof isemployed to described an instance were two or more groups may be thesame or different from each other and the occurrence of one group doesnot impact or influence the occurrence of the other group.

The term “alkyl” refers to a monovalent alkane (hydrocarbon) derivedradical containing from 1 to 18 carbon atoms unless otherwise defined.It may be straight or branched. Suitable straight or branched alkylgroups include methyl, ethyl, propyl, isopropyl, butyl, 3-butyl, andt-butyl. Alkyl also includes a straight or branched alkyl group thatcontains or is interrupted by a cycloalkane portion.

The term “alkenyl” refers to a hydrocarbon radical straight or branchedcontaining from 2 to 18 carbon atoms and at least one carbon to carbondouble bond. Preferably one carbon to carbon double bond is present, andup to four non-aromatic (non-resonating) carbon-carbon double bonds maybe present. Suitable alkenyl groups include ethenyl, propenyl, andbutenyl.

The term “alkynyl” refers to a hydrocarbon radical straight or branchedcontaining from 2 to 18 carbon atoms and at least one carbon to carbontriple bond. Up to three carbon-carbon triple bonds may be present.Suitable alkynyl groups include ethynyl, propynyl, and butynyl.

The term “alkoxy” refers to an alkyl group of indicated carbon atomsattached through an oxygen linkage.

The term “halogen” refers to fluorine, chlorine, bromine, iodine.

The term “halomethyl” refers to a carbon with one or more halogensubstituent.

The term “aryl” refers to a substituted aromatic hydrocarbon ring.Suitable aryl groups include single-ring, fused, and biphenyl aromatics.

The term “bridging group” refers to a moiety joining an aromatic and asilicon-containing functionality.

The term “arene” refers to an aromatic compound

The term “spacer” refers to a group between an aromatic and asilicon-containing functionality.

The term ‘OD’ or optical density refers to the optical absorbance of aculture measured at 600 nm.

The term ‘TLC’ refers to thin layer chromatography.

In accordance with an embodiment of the present invention, processesthat are effective in converting aryl silane substrates to silanecis-diols are provided, and silane cis-diol compositions are provided.Such processes include contacting a substrate, e.g., a compound ofFormulae I-I″″ as defined below, with a catalyst such as a dioxygenaseenzyme, and obtaining the desired cis-diol. The cis-diol may be obtainedby recovering the resulting compound of Formulae II-II″″ as definedbelow. The process may further include isolating and purifying theresulting compound. It is further contemplated that the resultingcompound could be used as an intermediate substrate useful in thepreparation of other derivatives or end-products.

The present invention provides a method for a biological production ofcis-diols from a fermentable silicon substrate by a microorganism grownwith a suitable carbon source. Examples of suitable carbon sourcesinclude, but are not limited to, glucose, fructose, sucrose or glyceroland mixtures thereof. The method comprises providing a dioxygenaseenzyme, contacting the dioxygenase enzyme with an aryl silane substrate,and obtaining a cis-diol from the growth media. The dioxygenase enzymemay be provided in any suitable manner. For example, the enzyme may bepresent in whole cells or cell-free. The term “whole cells” refers to aintact microorganism that expressed the desired enzymatic catalyst. Themicroorganism can be a wild type microorganism that is known to expressor produce the desired enzymatic catalyst, e.g., P. putida. The termcell free refers to an extract or solution of the desired enzymecatalyst. The enzyme may be provided in a wild-type microorganism or itmay be provided in a genetically altered organism harboring a geneencoding a dioxygenase enzyme. In addition to an appropriate aryl silanesubstrate, the fermentation media generally contains suitable carbonsources (hexoses such as glucose, pentoses such as fructose, etc.),minerals, salts, cofactors, buffers and other components, known to thoseskilled in the art, suitable for the growth of the cultures andpromotion of the enzymatic pathway necessary for cis-diol production.

Generally, cells are grown at appropriate temperatures and inappropriate media. Suitable growth media in the present invention areminimal mineral salts media to facilitate the subsequent extraction ofthe products. Suitable pH ranges for the fermentation are between pH 5.0to pH 9.0 where pH 6.8 to pH 8.0 is preferred as the initial condition.

In accordance with a further embodiment of the present invention, arylsilanes are dioxygenated to their corresponding cis-diols. Acorresponding cis-diol refers to the conversion of an aryl silanesubstrate by the attachment of two hydroxyl groups to adjacent carbonsin a cis configuration with respect to one another by the catalyticaction of a dioxygenase upon the substrate. The conversion of arylsilanes to the corresponding cis-dol derivatives results in the loss ofaromaticity of the ring that underwent dioxygenation. For purposes ofdefining and describing the present invention, “aryl silane” shall beunderstood as referring to a compound containing at least one aromaticring and at least one silicon atom. In one aspect the aromaticcomponents include substituted single ring, fused or biphenyl aromatics.Exemplary aromatic components include, but are not limited to, phenyl,naphthyl or biphenyl derivatives having a silicon-containing group.Other exemplary aromatics include, but are not limited to, thosecontaining additional fused heterocyclic or carbocyclic rings, e.g,silicon substituted indoles and/or indenes. The silicon atom can becontained in a silicon containing substituent, e.g. the silicon atom iseither directly attached to the aromatic ring or attached through aspacer element. Such aryl silanes are available through well knownsynthetic methods (e.g., Murata, M. et al. (2002) Rhodium(I)—CatalyzedSilylation of Aryl Halides with Triethoxysilane: Practical SyntheticRoute to Aryltriethoxysilanes. Org. Letters, Vol. 4, No. 11, pp1843-1845). Further contemplated by the present invention is thesubsequent conversion of silane cis-diols to the correspondingcatechols. A corresponding catechol refers to the conversion of acis-diol substrate by the dehydrogenation of the substrate by thecatalytic action of a diol dehydrogenase upon the substrate wherein thearomaticity is restored and results in the formation of a catecholderivative. A summation of these catalytic reactions is illustratedbelow:

The chemistry of silicon renders the intermediate silane cis-diols ofthe instant invention unique relative to the substituents described bythe prior art, which comprise carbon, halogen, or heteroatomfunctionalities. For example, the scientific literature records manyexamples of reactions that are particular to silicon and not thecorresponding carbon analogs. These reactions include hydrosilylation ofalkenes and ketones, the addition of electrophiles to vinyl and allylsilanes, and palladium catalyzed cross-coupling of vinyl silanes witharyl halides (Brook, M. A., Silicon in Organic, Organometallic andPolymer Chemistry (2000), Wiley). The silane cis-diols may be used: aschiral intermediates, for synthesizing polymers, as chiral separators,to form optically active materials, to act as carbohydrate analogs, andas intermediates in natural products synthesis.

In accordance with an embodiment of the present invention, a process isprovided for conversion of a compound of the Formula (I):

into a compound of the Formula (II):

using a dioxygenase enzyme;

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, an aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R; and    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³.

The present invention is not limited, however, to these particularsubstituents. It is therefore contemplated that the compounds ofFormulas (I) and (II) can include any substituent containing at leastone silicon atom and the silicon atom need not be directly bonded to thearomatic ring, which itself may be multiply substituted with a range offunctionality, including additional silicon-containing groups. Forexample, the silicon may be included as part of a chain of between 1 and18 carbons, including branched and unsaturated carbon chains with bothdouble and triple bonding attached to an arene moiety substituted with ahalogen or other group. Furthermore, the introduced hydroxyl groups neednot be directly adjacent to the group containing silicon. For example,such hydroxyl groups could one or more carbons removed from the groupcontaining silicon. The prior art records instances where theintroduction of additional functionality such as an iodo (I) group to amonosubstituted arene alters the regioselectivity of dihydroxylationwith respect to the initial functionality (see, for example, EP 717729B1or U.S. Pat. No. 5,763,689, both to Boyd et al.).

In one aspect of the present invention, R¹, R², and R³ are eachindependently selected from hydrogen, a linear or branched C₁-C₅ alkyl,a linear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl,halomethyl, or OR; and R is hydrogen, methyl, or ethyl. In anotheraspect of the present invention, R¹, R², and R³ are each independentlyselected from hydrogen, methyl, chloromethyl, or vinyl.

Examples of suitable aryl silane substrates and the correspondingcis-diols are shown below in Scheme 1. Scheme I. Conversion of arylsilanes to cis-diol products Aryl silane substrate cis-diol product 1a

2a

Dimethylphenylvinylsilane(1S,2S)-3-(dimethylvinylsilyl)cyclohexa-3,5-diene-1,2-diol 1b

2b

Dimethylphenylsilane(1S,2S)-1-(dimethylsilyl)cyclohexa-3,5-diene-1,2-diol 1c

2c

Phenyltrimethylsilane(1S,2S)-3-(trimethylsilyl)cyclohexa-3,5-diene-1,2-diol 1d

2d

Benzyltrimethylsilane(1S,2R)-3-(trimethylsilylmethyl)cyclohexa-3,5-diene-1,2-diol 1e

2e

(R,S)-methylphenylvinylsilane(1S,2S)-1-[(R,S)-methylvinylsilyl]cyclohexa-3,5-diene-1,2-diol 1f

2f

(Chloromethyl)dimethylphenylsilane(1S,2S)-3-[(chloromethyl)dimethylsilyl]cyclohexa-3,5-diene-1,2-diol

In accordance with another aspect of the present invention, a process isprovided for conversion of a compound of the Formula (I′):

into a compound of the Formula (II′):

using a dioxygenase enzyme;

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties; n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³;    -   X is a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl,        or C₂-C₁₈ alkynyl spacer.        However, when X═C₂ alkynyl and R¹═R²═R³ then R¹═R²═R³ cannot be        —CH₃.

This aspect of the present invention is also intended to apply wherecompounds of formulas (I′) and (II′) occur in the context of a polymerlinked through one of more of the functionalities R and R¹—R⁴. Forexample, the arene units of a diblock copolymer consisting ofpolydimethylsiloxane (PDMS) and polyphenylmethylsiloxane (PPMS) could bewholly or partially converted to the corresponding cis-diols.

In one embodiment, R¹, R², and R³ are each independently selected fromhydrogen, a linear or branched C₁-C₅ alkyl, a linear or branched C₂-C₅alkenyl, a linear or branched C₂-C₅ alkynyl, halomethyl, or OR; R⁴ isselected from hydrogen, halogen, a linear or branched C₁-C₅ alkyl, alinear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl,CN, NO₂, OR or SiR¹R²R³; R is hydrogen, methyl, or ethyl; and X iseither a divalent linear or branched C₁-C₅ alkyl, C₂-C₅ alkenyl, orC₂-C₅ alkynyl spacer. In yet another embodiment, R¹, R², and R³ are eachindependently selected from hydrogen, methyl, chloromethyl, or vinyl andR⁴ is selected from hydrogen, halogen, a linear or branched C₁-C₃ alkyl,a linear or branched C₂-C₃ alkenyl, a linear or branched C₂-C₃ alkynyl,CN, NO₂, OR or SiR¹R²R³.

In accordance with still another aspect of the present invention, aprocess is provided for conversion of a compound of the Formula (I″):

into a compound of the Formula (II″):

using a dioxygenase enzyme;

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties;    -   n is 0-5; and    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³.

In one embodiment, R¹, R², and R³ are each independently selected fromhydrogen, a linear or branched C₁-C₅ alkyl, a linear or branched C₂-C₅alkenyl, a linear or branched C₂-C₅ alkynyl, halomethyl, or OR; R⁴ isselected from hydrogen, halogen, a linear or branched C₁-C₅ alkyl, alinear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl,CN, NO₂, OR or SiR¹R²R³; and R is hydrogen, methyl, or ethyl. In yetanother embodiment, R¹, R², and R³ are each independently selected fromhydrogen, methyl, chloromethyl, or vinyl and R⁴ is selected fromhydrogen, halogen, a linear or branched C₁-C₃ alkyl, a linear orbranched C₂-C₃ alkenyl, a linear or branched C₂-C₃ alkynyl, CN, NO₂, ORor SiR¹R²R³.

In accordance with still another aspect of the present invention, aprocess is provided for conversion of a compound of the Formula (I′″):

into a compound of the Formula (II′″):

using a dioxygenase enzyme;

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties;    -   n is 0-5; and    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³.

In one embodiment, R¹, R², and R³ are each independently selected fromhydrogen, a linear or branched C₁-C₅ alkyl, a linear or branched C₂-C₅alkenyl, a linear or branched C₂-C₅ alkynyl, halomethyl, or OR; R⁴ isselected from hydrogen, halogen, a linear or branched C₁-C₅ alkyl, alinear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl,CN, NO₂, OR or SiR¹R²R³; and R is hydrogen, methyl, or ethyl. In yetanother embodiment, R¹, R², and R³ are each independently selected fromhydrogen, methyl, chloromethyl, or vinyl and R⁴ is selected fromhydrogen, halogen, a linear or branched C₁-C₃ alkyl, a linear orbranched C₂-C₃ alkenyl, a linear or branched C₂-C₃ alkynyl, CN, NO₂, ORor SiR¹R²R³.

In accordance with still another aspect of the present invention, aprocess is provided for conversion of a compound of the Formula (I″″):

into a compound of the Formula (II″″):

using a dioxygenase enzyme;

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties;    -   n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl,        C₂-C₁₈ alkynyl spacer, S, O or NR₁₋₂.        The two hydroxyl group substituents are attached to adjacent        carbons and are in a cis-configuration with respect to one        another.

In one embodiment, R¹, R², and R³ are each independently selected fromhydrogen, a linear or branched C₁-C₅ alkyl, a linear or branched C₂-C₅alkenyl, a linear or branched C₂-C₅ alkynyl, halomethyl, or OR; R⁴ isselected from hydrogen, halogen, a linear or branched C₁-C₅ alkyl, alinear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl,CN, NO₂, OR or SiR¹R²R³; R is hydrogen, methyl, or ethyl; and X iseither a divalent linear or branched C₁-C₅ alkyl, C₂-C₅ alkenyl, orC₂-C₅ alkynyl spacer. In yet another embodiment, R¹, R², and R³ are eachindependently selected from hydrogen, methyl, chloromethyl, or vinyl andR⁴ is selected from hydrogen, halogen, a linear or branched C₁-C₃ alkyl,a linear or branched C₂-C₃ alkenyl, a linear or branched C₂-C₃ alkynyl,CN, NO₂, OR or SiR¹R²R³.

It will be understood by those having skill in the art that thecompounds of Formula (II)-(II″″) comprise a novel class of chiralcis-diols containing silicon. It will be further understood that thepresent invention encompasses the compounds of Formula (II)-(II″″). Thecis-diol may be present in an enantiomeric excess of between about 10 toabout 100 percent. Alternatively, the cis-diol may be present in anenantiomeric excess of between about 70 to about 100 percent, or greaterthan about 95 percent, or greater than about 98 percent. It will befurther understood that the methods of the present invention maycomprise providing a plurality of aryl silane substrates. The pluralityof aryl silane substrates comprise the same aryl silane, or theplurality of aryl silane substrates comprise different aryl silanes.

The dioxygenase enzyme can be any aromatic dioxygenase enzyme,recombinant or otherwise; for example toluene dioxygenase (EC1.14.12.11), naphthalene dioxygenase (EC 1.14.12.12), biphenyldioxygenase (EC 1.14.12.18). It is contemplated that the dioxygenaseenzyme that contacts the substrate can be in any form that effectivelytransforms a compound of Formula (I)-(I″″) into a compound of Formula(II)-(II″″), respectively. For example, the aromatic dioxygenase enzymecan be in the form of a cell-free extract, a synthetic form,disintegrated cells, or whole cells. For example, the dioxygenase enzymeis present in whole cells in various strains of E. coli, which expressthe toluene dioxygenase enzyme from P. putida. The construction of hostcells expressing toluene dioxygenase JM109 (SEQ ID No. 1), e.g.,containing a plasmid that expresses toluene dioxygenase is described inZylstra, G. J. and Gibson, D. T., Toluene degradation by Pseudomonasputida F1, Nucleotide sequence of the todC1C2BADE genes and theirexpression in Escherichia coli, J. Biol. Chem. 264: 14940-14946 (1989),which is incorporated by reference herein. The nucleotide sequence of P.putida toluene dioxygenase and cis-toluene dihydrodiol dehydrogenase(todC1C2BAD) is given below (SEQ ID No. 1) and has an accession numberof J04996. 1 gaattcgttc ggcggtgcct tgtctctggc ctttgctatc cgatttccgcatcgggttcg 61 ccgcctggtg ctgatgggtg ccgttggcgt gagcttcgag ctcacggatggactggatgc 121 agtttggggt tatgagccgt ccgtgccgaa catgcgcaag gtcatggactacttcgccta 181 cgaccgaagt ctcgtttccg acgaactggc ggaactgcgc tacaaggcgagcacccggcc 241 cggttttcag gaggccttcg cttccatgtt ccctgctccg cggcagcgctgggtagatgc 301 gctggccagt tccgatcagg acatccggga catccggcat gaaacgctgatcctgcatgg 361 ccgcgacgat cgcgtgattc ccctcgaaac ctcgttgcgg ctgaaccagctgatcgaacc 421 ctcccagtta catgtctttg gcaggtgtgg ccattgggtg cagatcgagcaaaaccgggg 481 ctttatccgc ttggtcaacg attttcttgc cgcggaggac tgatcgcaaaaacgggaatg 541 accatccgtt ctgaaagcac gtcatcggca attgcctgcc aagtacccgccatccactac 601 cttgaaaagt gagaagacaa tgaatcagac cgacacatca cctatcaggctgcgcaggag 661 ctggaacacc agcgagatag aagcgctctt tgacgagcat gccggacgtatcgatccgcg 721 catttatacc gatgaggatc tgtaccaact cgaactggag cgtgtcttcgcccggtcctg 781 gctgctgttg gggcatgaaa cccagattcg caagccgggc gattacatcacgacctacat 841 gggtgaagac cctgtcgtgg tcgtccggca gaaagacgcc agcattgccgtgttcctgaa 901 ccagtgccgc caccgtggca tgcgcatctg ccgcgcggat gccggaaacgcgaaggcgtt 961 cacttgcagc taccacgggt gggcttacga caccgccggc aatcttgtcaatgtgcctta 1021 cgaggccgaa tccttcgcgt gcctgaacaa gaaggaatgg agcccgctgaaggcccgggt 1081 agaaacctac aagggcctga ttttcgccaa ctgggatgag aacgctgtagacctcgacac 1141 gtatctgggc gaggcgaagt tctacatgga ccacatgctc gaccgcaccgaggccggcac 1201 cgaagcgatc ccgggcgtgc agaagtgggt cattccctgt aactggaaattcgccgcaga 1261 gcagttttgc agcgacatgt accatgccgg gacgacctcg catctgtctggcatcctggc 1321 aggcctgcca gaagaccttg aaatggccga ccttgctccg ccgacagttggcaagcagta 1381 ccgtgcgtca tggggcggac atggaagtgg cttctatgtc ggcgaccccaatctgatgct 1441 tgccatcatg gggccaaagg tcaccagcta ctggaccgaa ggccccgcgtcggaaaaggc 1501 ggccgaacgt ctgggtagcg tggagcgcgg ctcgaaactc atggtcgagcacatgaccgt 1561 cttccccacg tgttccttcc tcccaggtat caatacggtc cggacatggcatccgcgcgg 1621 gccgaacgag gtcgaggtat gggcgtttac ggtggtcgat gctgatgctcctgacgatat 1681 caaggaagag ttccggcgcc agacgctgcg caccttctct gccggtggcgtgttcgagca 1741 ggacgacggg gagaactggg tcgagatcca gcacatcctg cgaggccacaggcgcggag 1801 ccgccctttc aatgccgaga tgagcatgga ccagaccgtc gacaacgacccggtttaccc 1861 cgggcggatc agcaacaacg tctacagcga ggaagctgcc cgcgggctctatgcccattg 1921 gctgcggatg atgacatccc ccgactggga cgcgctgaag gcgacacgctgaatccagag 1981 acagcttgcg ccacgcagtg gcgccggcca gaggccgcat ttgacttcgacccaggttgg 2041 atgcggtgga ccttgtccat ttgaaatcta caaggaacga ccatgattgattcagccaac 2101 agagccgacg tctttctccg caagccggca cccgtagcgc ccgaactgcagcacgaagtc 2161 gagcagttct actattggga ggccaagctt ctcaacgatc gccgcttcgaggagtggttc 2221 gcgctgctcg cggaagacat tcactacttc atgcccattc gcaccacgcggatcatgcgg 2281 gactcgcgcc ttgaatactc aggctcccga gagtacgcgc acttcgatgacgacgccacg 2341 atgatgaagg gacgcttgcg caagatcacg tccgacgtga gctggtccgagaaccccgca 2401 tcgcggaccc ggcatctcgt gagcaacgtg atgatcgtcg gcgcagaggcagaaggggag 2461 tacgaaatct caagcgcctt cattgtgtac cgcaatcgtc tggagcggcagctcgacatc 2521 tttgccggtg agcgtcgcga tacgttgcgc cgtaacacga gcgaggccgggttcgagatc 2581 gtcaatcgga ccatcctgat cgaccagagc accatcctgg ccaataacctcagtttcttc 2641 ttctaggtga tgtcatgact tggacataca tattgcggca gggtgacctgccacccggtg 2701 agatgcagcg ctacgaaggc ggcccggaac ctgtgatggt ctgcaacgtcgatggcgagt 2761 tcttcgcggt gcaggatacc tgcacgcatg gggactgggc gttgtcggatggttacctgg 2821 acggtgatat tgtcgaatgc acgttgcatt tcggcaagtt ctgcgtgcggaccgggaagg 2881 tgaaggcgct gcctgcttgc aaacctatca aggtattccc aatcaaggtcgaaggcgatg 2941 aagtgcacgt cgatctcgac aacggggagt tgaagtgatg gctacccatgtggcgatcat 3001 cggcaatggc gtgggtggct tcacgaccgc gcaggcccta cgtgccgagggcttcgaggg 3061 gagaatctcg ctgattgggg acgaaccgca tctcccctat gaccgaccatccttgtccaa 3121 ggcggttctc gacggcagcc ttgagcggcc gcccatactg gccgaggccgattggtacgg 3181 cgaggcccgc atcgacatgc tgaccggccc ggaagtcact gcccttgatgtgcagacaag 3241 gacgatcagt ctggatgatg gcaccacgct ctctgcggac gccatcgtcatcgcgacggg 3301 cagtcgagcg cggacgatgg cgttgcccgg cagccaactg cccggcgtcgtaacgctgcg 3361 cacctacggt gacgtgcagg tattgcgcga tagttggact tccgcgacgcggctgctgat 3421 tgtgggtggc ggattgatcg gctgcgaggt cgcgacgacg gcgcgcaagctcggcctgtc 3481 ggtcacgatc ctggaggcag gtgatgaact gctggtccga gtacttgggcggcgtatcgg 3541 tgcctggctg cgcggcctgc tgacagaact tggtgtgcag gtcgagttgggaacgggtgt 3601 cgtaggtttt tctggtgagg gccagctcga acaagtcatg gccagcgatgggcgcagctt 3661 cgtagccgat agcgcactca tttgcgtcgg cgcggagccc gcggatcaacttgcgcgtca 3721 agcgggcttg gcatgtgacc gcggcgtcat tgtcgatcac tgcggtgcgacgcttgccaa 3781 aggcgtattc gccgtcggag atgtggccag ttggccgctg cgcgccggcggccggcgttc 3841 gctcgaaacc tatatgaacg cgcagcgcca agccgccgcg gtggctgcggccattctggg 3901 gaaaaacgta tcggcaccgc aactgcccgt gtcctggacg gagatcgctgggcatcgcat 3961 gcagatggcg ggcgatatcg aaggacctgg tgatttcgtc tcgcgcggcatgcccggtag 4021 tggcgctgcc ctgttgttcc gcctgcagga gcgaaggatt caggcggtcgtcgcggtcga 4081 tgcaccccgt gacttcgcgc ttgcaacccg attggtagaa gcccgcgcggcaatcgagcc 4141 agcacggctg gcagatcttt caaacagtat gcgcgatttt gttcgtgcgaatgaaggaga 4201 cctaacgtga gacttgaagg cgaagtggcc ttggtgacag gcggtggcgcaggcctgggc 4261 agagcgatcg tggatcgtta tgtcgcggaa ggtgcgcgtg tcgcggtgctggataaatcc 4321 gcggcaggcc tggaagcgct caggaaactc catggcgatg caatcgtgggcgtggagggg 4381 gatgttcgct cgctcgacag ccatcgtgag gctgtggccc gctgcgtcgaagcgttcggc 4441 aagctggact gcctggttgg caatgctggc gtttgggact acctgacccaactggtggat 4501 attcccgacg acctcatatc ggaggcattc gaggaaatgt tcgaggtcaatgtcaagggc 4561 tacatcctgg cggcaaaggc tgcgctacct gcgctttatc agagcaaaggcagcgcgata 4621 ttcactgtgt cgaatgccgg tttctacccg ggcggtggcg gtgttctgtatacagctggc 4681 aaacatgccg tgattggatt gatcaagcag ctcgcgcacg aatgggggccgcgtatccgc 4741 gtcaacggca tcgcccccgg tggcattttg gggagcgatc tgcgcgggctgaagagcctt 4801 gatttacaag acaagagcat ttcgaccttt ccattggacg acatgctgaaatccgttctt 4861 ccgaccgggc gggccgccac tgccgaggaa tacgccggcg cctatgtcttcttcgcgacg 4921 cgcggcgaca cggttccgct caccggtagc gtgttgaact tcgatggcggcatgggcgtg 4981 cgtggcttgt tcgaagccag cctaggcgca cagctcgaca agcacttcggttga

Additionally, the deduced amino acid sequences of P. putida toluenedioxygenase (iron-sulfur protein, ferredoxin, reductase) are givenbelow:

Iron-sulfur protein large subunit (todC1) (SEQ ID No. 2)

Start:620 Stop:197

translation= “MNQTDTSPIRLRRSWNTSEIEALFDEHAGRIDPRIYTDEDLYQLELERVFARSWLLLGHETQIRKPGDYITTYMGEDPVVVVRQKDASIAVFLNQCRHRGMRICRADAGNAKAFTCSYHGWAYDTAGNLVNVPYEAESFACLNKKEWSPLKARVETYKGLIFANWDENAVDLDTYLGEAKFYMDHMLDRTEAGTEAIPGVQKWVIPCNWKFAAEQFCSDMYHAGTTSHLSGILAGLPEDLEMADLAPPTVGKQYRASWGGHGSGFYVGDPNLMLAIMGPKVTSYWTEGPASEKAAERLGSVERGSKLMVEHMTVFPTCSFLPGINTVRTWHPRGPNEVEVWAFTVVDADAPDDIKEEFRRQTLRTFSAGGVFEQDDGENWVEIQHILRGHKARSRPFNAEMSMDQTVDNDPVYPGRISNNVYSEEAARGLYAHWLRMMTSPDWDALKAT R”Iron-sulfur protein small subunit (todC2) (SEQ ID No. 3)Start:2083 Stop:2646

translation= “MIDSANRADVFLRKPAPVAPELQHEVEQFYYWEAKLLNDRRFEEWFALLAEDIHYFMPIRTTRIMRDSRLEYSGSREYAHFDDDATMMKGRLRKITSDVSWSENPASRTRHLVSNVMIVGAEAEGEYEISSAFIVYRNRLERQLDIFAGERRDTLRRNTSEAGFEIVNRTILIDQSTILANNLSFFF”Ferredoxin (todB) (SEQ ID No. 4)Start:2655 Stop:2978

translation= “MTWTYILRQGDLPPGEMQRYEGGPEPVMVCNVDGEFFAVQDTCTHGDWALSDGYLDGDIVECTLHFGKFCVRTGKVKALPACKPIKVFPIKVEGDEVHV DLDNGELK”Reductase (todA) (SEQ ID No. 5)Start:2978 Stop:4210

translation= “MATHVAIIGNGVGGFTTAQALRAEGFEGRISLIGDEPHLPYDRPSLSKAVLDGSLERPPILAEADWYGEARIDMLTGPEVTALDVQTRTISLDDGTTLSADAIVIATGSRARTMALPGSQLPGVVTLRTYGDVQVLRDSWTSATRLLIVGGGLIGCEVTARKLGLSVTILEAGDELLVRVLGRRIGAWLRGLLTELGVQVELGTGVVGFSGEGQLEQVMASDGRSFVADSALICVGAEPADQLARQAGLACDRGVIVDHCGATLAKGVFAVGDVASWPLRAGGRRSLETYMNAQRQAAAVAAAILGKNVSAPQLPVSWTEIAGHRMQMAGDIEGPGDFVSRGMPGSGAALLFRLQERRIQAVVAVDAPRDFALATRLVEARAAIEPARLADLSNSMRDF VRANEGDLT”Cis-toluene dihydrodiol dehydrogenase (todD, gtg start codon) (SEQ IDNo. 6)Start:4207 Stop:5034

translation= “MRLEGEVALVTGGGAGLGRAIVDRYVAEGARVAVLDKSAAGLEALRKLHGDAIVGVEGDVRSLDSHREAVARCVEAFGKLDCLVGNAGVWDYLTQLVDIPDDLISEAFEEMFEVNVKGYILAAKAALPALYQSKGSAIFTVSNAGFYPGGGGVLYTAGKHAVIGLIKQLAHEWGPRIRVNGIAPGGILGSDLRGLKSLDLQDKSISTFPLDDMLKSVLPTGRAATAEEYAGAYVFFATRGDTVPLTGSVLNFDGGMGVRGLFEASLGAQLDKHFG”In addition, the construction of host cells expressing naphthalenedioxygenase and biphenyl dioxygenase are described in Simon, M., et alGene, 127:31-37 (1993); Mondello, F., J. Bacteriology, 171(3):1725-1732(1989). U.S. Pat. No. 5,173,425 teaches a method for overexpressing adioxygenase, and it is incorporated by reference herein.

The following dioxygenase-containing organisms can be contacted with thesubstrates, used to oxidize aryl silanes via enzymatic dioxygenation totheir corresponding cis-diols (Whited, G. M. et al. (1994) Oxidation of2-Methoxynaphthalene by Toluene, Naphthalene and Biphenyl Dioxygenases:Structure and Absolute Stereochemistry of Metabolites. Bioorganic &Medicinal Chemistry, Vol. 2, No. 7, pp. 727-734): Strain Phenotype E.coli JM109 containing the structural genes for JM109(pDTG601) toluenedioxygenase (todC1C2BA) from Pseudomonas putida F1 in pKK223-3;dioxygenase is inducible by isopropyl- β-D-thiogalactoside (IPTG);ampicillin and carbenicillen resistant (Amp). E. coli JM109 containingthe structural genes for JM109(pDTG602) toluene dioxygenase and(+)-cis-(1S,2R)- dihydroxy-3-methylcyclohexa-3,5-diene dehydrogenase(todC1C2BAD) from Pseudomonas putida F1 in pKK223-3; dioxygenase isinducible by isopropyl- β-D-thiogalactoside (IPTG); ampicillin andcarbenicillen resistant (Amp). Ralstonia Wild strain containingpolychlorinated eutropha A5 biphenyl (PCB) catabolic genes SphingomonasMutant strain containing PCB/biphenyl yanoikuyae B8/36 catabolic genesin which dihydrodiol dehydrogenase (bphB) has been inactivated E. coliC534 containing the structural genes for C534(ProR/Sac) naphthalenedioxygenase from PpG7 (nahAaAbAcAd) in pAC1; dioxygenase is expressedconstitutively (Lambda P_(L) promoter); Amp.

The process of this aspect of the present invention can be viewed as abiological production process wherein the compounds of Formulas(I)-(I″″) (a group of aryl silanes) are converted into compounds ofFormulas (II)-(II″″), respectively, (a novel class of silane cis-diols)using a dioxygenase enzyme. It should be recognized that the absolutestereochemistry of the cis-diol products can vary according to thedioxygenase used (Aldrichimica Acta, Vol. 32, No. 2, pp. 35-62). Theprocess may be carried out in a liquid medium, more specifically, abuffered aqueous medium. Suitable buffers can be inorganic or organicand are typically those that control the pH of the medium in the rangeof between about 6 and about 8. For example, the buffer may be aninorganic, alkali metal phosphate buffer such as a 100 mM phosphatebuffer. The pH of the process may be maintained at a pH of about 6.8 byintermittent feeding of an inorganic base, which may be an alkali metalhydroxide such as dilute aqueous sodium or potassium hydroxide.

A co-substrate that provides for NADH recycle may optionally be added tothe liquid medium. Typically, this co-substrate is a sugar or othercarbon source (e.g. glycerol), which provides an economical energysource for the enzyme-producing microorganisms. Other optionalco-substrates include α-ketoacids and their alkali metal salts (e.g.,pyruvic acid and sodium pyruvate) and alcohols (e.g., ethanol andisopropanol).

The process involves oxidation of the compounds of Formulas (I)-(I″″)and the source of oxygen may be molecular oxygen (O₂). Therefore, duringthe process oxygen may be continuously introduced through the liquidmedium. For example, the oxygen may be in the form of air. The processmay be performed at a temperature from about 25° C. to about 50° C. orbetween about 30° C. and about 40° C. It will be understood that thecells of the present invention should be fed under conditions that allowthe cells to sufficiently metabolize the food source and to optimize theproduction of the cis-diols.

When the process has proceeded for a suitable period it may beterminated by any appropriate means, for example by centrifugation orfiltration and/or by cooling the broth to a temperature of less thanabout 5° C. The supernatant or product of Formulas (II)-(II″″) may beisolated by any convenient means, for example by solvent extraction,typically using a halocarbon solvent (e.g., CH₂Cl₂), an aromatic solvent(e.g., toluene) or an ester (e.g., ethyl acetate) following saturationwith sodium chloride. The organic extract can then be dried over sodiumsulfate, filtered and dried under vacuum.

In accordance with the present invention, the cis-diol-containing mediacan then be purified or further isolated to provide the cis-diolcomposition of the present invention. The inventors contemplate“isolated” as being greater than 90% [pure]. Suitable methods ofpurification include, but are not limited to biphasic extraction (e.g.,aqueous/organic phase extraction), recrystallization from solvents andsolvent mixtures known to those of skill in the art, ion exchange suchas through a column containing DOWEX® resin, elution chromatography andcombinations thereof. Methods of elution chromatography include, but arenot limited to preparative thin-layer chromatography, conventionalsilica gel chromatography, and high performance liquid chromatography.Purification of the cis-diol-containing compositions by any of the abovementioned means may optionally separate the residue into variousfractions, each of which may function alone or in combination with anyother fraction or fractions as the cis-diols of the present invention.

According to the next aspect of the present invention there is provideda process for the chemical conversion of the cis-diols into more stableacetonide derivatives. In accordance with one embodiment of the presentinvention, a compound of Formula (II) is converted into the more stableacetonide derivatives of the compound of Formula (III):

in which R¹, R², and R³ are as hereinbefore defined, by reaction of thecompound of Formula (II) with 2,2-dimethoxypropane or equivalentreagents (e.g. 2-methoxypropene). However, when R¹═R²═R³ then R¹═R²═R³cannot be —CH₃.

The compounds of Formula (II) may be supplied in a solution of2,2-dimethoxypropane, which may also contain trace amounts of Amberlite118-H⁺ acid resin. The reaction generally takes place over a period ofseveral hours. The reaction mixture may then be filtered, followed byevaporation of the solvent. The crude acetonides produced by the instantprocess of the present invention can be purified by any appropriatemethod.

The instant conversion reaction of silane cis-diols (the compound ofFormula (II)) to the acetonide derivatives (the compound of Formula(III)) is illustrated in the diagram below.

Confirmation of the identity of the acetonide derivative compounds maybe obtained by analysis of ¹H and ¹³C NMR spectra. The present inventionincludes the compounds produced by this transformation.

Examples of suitable cis-diol substrates and the corresponding acetonidederivatives are shown below in Scheme 2. Scheme 2. Acetonide derivativesof cis-diols cis-diol substrate Acetonide derivative 2a

3a

2b

3b

2c

3c

2d

3d

2e

3e

2f

3f

In accordance with one embodiment of the present invention, a compoundof Formula (II′) is converted into the more stable acetonide derivativesof the compound of Formula (III′):

in which R¹, R², R³, R⁴, X, and n are as hereinbefore defined, byreaction of the compound of Formula (II′) with 2,2-dimethoxypropane orequivalent reagents (e.g. 2-methoxypropene). However, when X═C₂ alkynyland R¹═R²═R³ then R¹═R²═R³ cannot be —CH₃.

In accordance with one embodiment of the present invention, a compoundof Formula (II″) is converted into the more stable acetonide derivativesof the compound of Formula (III″):

in which R¹, R², R³, R⁴, and n are as hereinbefore defined, by reactionof the compound of Formula (II″) with 2,2-dimethoxypropane or equivalentreagents (e.g. 2-methoxypropene).

In accordance with one embodiment of the present invention, a compoundof Formula (II′″) is converted into the more stable acetonidederivatives of the compound of Formula (III′″):

in which R¹, R², R³, R⁴, and n are as hereinbefore defined, by reactionof the compound of Formula (II′″) with 2,2-dimethoxypropane orequivalent reagents (e.g. 2-methoxypropene).

In accordance with one embodiment of the present invention, a compoundof Formula (II″″) is converted into the more stable acetonidederivatives of the compound of Formula (III″″):

in which R¹, R², R³, R⁴, X, and n are as hereinbefore defined, byreaction of the compound of Formula (I″″) with 2,2-dimethoxypropane orequivalent reagents (e.g. 2-methoxypropene).

In accordance with the present invention, further contemplated is theconversion of aryl silanes to catechols through the cis-diols. Inaccordance with one embodiment of the present invention an aryl silaneof Formula (I) is converted to a catechol of Formula (IV) through thecis-diols compounds of Formula (II). The process results in thebiocatalytic synthesis of a compound of Formula (IV):

in which R¹, R², and R³ are as hereinbefore defined, by reaction of thecompound of Formula (II) with a diol dehydrogenase enzyme. It iscontemplated that a strain of E. coli possessing both the toluenedioxygenase gene as well as a diol dehydrogenase gene can be used toconvert aryl silanes (the compounds of Formula (I)) to the correspondingcatechols (the compounds of Formula (IV)). Suitable diol dehydrogenasesmay be found in E.C. 1.3.1.19. For example the plasmid TDTG602 which mayhave the gene todC12BAD may be used in accordance with the presentinvention. Suitable diol dehydrogenases are found in Zylstra, G. J. andGibson, D. T., Toluene degradation by Pseudomonas putida F1, Nucleotidesequence of the todC1C2BADE genes and their expression in Escherichiacoli J. Biol. Chem. 264: 14940-14946 (1989), which is incorporated byreference herein.

Examples of suitable cis-diol substrates and the corresponding catecholsare shown below in Scheme 3. Scheme 3. Conversion of silane cis-diols tosilane catechols cis-diol substrate Catechol derivative 2a

4a

2b

4b

In accordance with one embodiment of the present invention an arylsilane of formula (I′) is converted to a catechol of formula (IV′)through the cis-diols compounds of Formula (II′). The process results inthe biocatalytic synthesis of a compound of Formula (IV′):

in which R¹, R², R³, R⁴, X, and n are as hereinbefore defined, byreaction of the compound of Formula (II′) with a diol dehydrogenaseenzyme.

In accordance with one embodiment of the present invention an arylsilane of formula (I″) is converted to a catechol of formula (IV″)through the cis-diols compounds of Formula (II″). The process results inthe biocatalytic synthesis of a compound of Formula (IV″):

in which R¹, R², R³, R⁴ and n are as hereinbefore defined, by reactionof the compound of Formula (II″) with a diol dehydrogenase enzyme.

In accordance with one embodiment of the present invention an arylsilane of formula (I′″) is converted to a catechol of formula (IV′″)through the cis-diols compounds of Formula (II′″). The process resultsin the biocatalytic synthesis of a compound of Formula (IV′″):

in which R¹, R², R³, R⁴ and n are as hereinbefore defined, by reactionof the compound of Formula (II′″) with a diol dehydrogenase enzyme.

In accordance with one embodiment of the present invention an arylsilane of Formula (I″″) is converted to a catechol of Formula (IV″″)through the cis-diols compounds of Formula (II″″). The process resultsin the biocatalytic synthesis of a compound of Formula (IV″″):

in which R¹, R², R³, R⁴, X and n are as hereinbefore defined, byreaction of the compound of Formula (II′) with a diol dehydrogenaseenzyme.

In accordance with the present invention, the transformation ofadditional aryl silanes to cis-diols, including bis-aryl silanes such as2-(diphenylmethylsilyl)ethanol and the compounds produced thereby, isfurther contemplated. The oxidation of a single aryl ring will result inmaterials possessing chirality around the silicon atom, as well as twonew stereogenic carbon centers.

In accordance with the present invention, further contemplated areadditional chemical transformations of the cis-diols and acetonides ofthe present invention. In accordance with one aspect of the presentinvention, the cis-diol acetonides may be used to form cycloadducts byallowing the concentrated cis-diol acetonide to stand at roomtemperature. For example, Scheme 4 illustrates the formation ofcycloadducts.

It will be understood that the cis-diol acetonides of Formulas(III)-(III″″) may be used to form cycloadducts in accordance with thepresent invention.

In accordance with another aspect of the present invention thederivatization or reaction of the hydroxyl groups of the cis-diol iscontemplated. Suitable methods for the derivatization and protection aredetailed in T. W. Greene and P. G. M. Wits, Protective Groups in OrganicSynthesis, 3^(rd) ed. (1999), Wiley, New York and is incorporated byreference herein. For example, as discussed above, the hydroxyl groupsof the cis-diols may be derivatized to form the acetonides of Formulas(III-III″″). Additionally, the hydroxyl groups of the cis-diols may bederivatized using any alkylidene group in a manner similar to theformation of the acetonides. The alkylidene may be any suitablealkylidene. For example, the alkylidene may be benzyldene or ethylidene.

In another example, at least one of the hydroxyl groups of the cis-diolmay be removed. For example, the cis-diols may be reacted to givephenols of the formula

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties; n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³;    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.        However, when X=nothing then R¹, R², and R³ cannot be R¹═R²═CH₃        and R³═H or R¹═R²═R³═CH₃.        For example, the derivatives may be of the formula        which may be made by reacting the appropriate cis-diol with H⁺        in water.

In a further example, the hydroxyl groups of the cis-diols may bederivatized to form a di-O-acyl derivative. The acyl may be any suitableacyl functionality. For example, the acyl may be a linear or branchedC₁-C₁₈ alkyl, a linear or branched C₂-C₁₈ alkenyl, or a linear orbranched C₂-C₁₈ alkynyl. For example, the di-O-acyl derivative may be aderivative of the formula:

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties; n is 0-3;    -   R⁵ is linear or branched C₁-C₁₈ alkyl, halomethyl, linear or        branched C₂-C₁₈ alkenyl, or linear or branched C₂-C₁₈ alkynyl;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.        For example, the di-O-acyl may be        which may be made by reacting dimethylsilyl cyclohexadiene        cis-diol (2b) with pyridine and acetic anhydride and then        extracting the reaction mixture with ethyl acetate.

In yet another example, the hydroxyl groups of the cis-diol could bederivatized to form a silyl ether. For example, the silyl ether may be aderivative of the formula:

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₃,        O(CO)R, SiR¹R²R³, or a bridging group between two arene or        substituted arene moieties;    -   n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, or C₂-C₁₈ alkynyl spacer.        For example, the silyl ether may be        which may be made by reacting dimethylsilyl cyclohexadiene        cis-diol (2b) with t-BuMe₂SiCl, dimethylformamide, and        imidazole.

In a further example, the hydroxy groups of the cis-diols may bederivatized by forming a boronate ester. For example, the boronate estermay be an ester of the formula

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties; n is 0-3;    -   R⁵ is aryl, linear or branched C₁-C₁₈ alkyl, linear or branched        C₂-C₁₈ alkenyl, or linear or branched C₂-C₁₈ alkynyl;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.        For example, the boronate ester may be        which may be made by reacting dimethylsilyl cyclohexadiene        cis-diol (2b) with phenylboronic acid (PhB(OH)₂).

In accordance with another aspect of the present invention the oxidationof the double bonds of the cis-diols and acetonides of the presentinvention to the corresponding epoxy derivatives is contemplated. Forexample, the cis-diol may have the double bond oxidized to form epoxyderivatives of the formulas:

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₃,        O(CO)R, SiR¹R²R³, or a bridging group between two arene or        substituted arene moieties;    -   n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.        For example, the epoxy derivatives may be        which may be made by reacting dimethylsilyl cyclohexadiene        cis-diol (2b) with m-choloroperbenzoic acid (m-CPBA).

For example, the acetonides of the present invention may have the doublebond oxidized to form epoxy derivatives of the formulas:

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₃,        O(CO)R, SiR¹R²R³, or a bridging group between two arene or        substituted arene moieties;    -   n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.        However, when X=nothing then R¹, R², and R³ cannot be        R¹═R²═R³═CH₃.        For example, the epoxy derivatives may be        wherein R═H and OH.        which may be made by reacting dimethylsilyl cyclohexadiene        cis-diol acetonide (3b) with m-CPBA.

In accordance with another aspect of the present invention the reductionof one or both of the double bonds of the cis-diols and acetonides ofthe present invention to the corresponding partially or fully saturatedmaterials are contemplated. For example, the cis-diol may have at leastone of the double bonds reduced to form partially or fully saturatedmaterial of the formulas:

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties;    -   n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.        For example, the partially or fully saturated derivatives may be

which may be made by exposing dimethylsilyl cyclohexadiene cis-diol (2b)to hydrogen gas or through the diimide procedure using potassiumazodicarbonamide in acetic acid. (Pasto., D. J. “Reduction with Diimide”Organic. Reactions, 1991, 40, 91.)

For example, the acetonide may have at least one the double bondsreduced to form partially or fully saturated material of the formulas:

wherein:

-   -   R¹, R², and R³ are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties;    -   n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.        For example, the derivative may be        which may be made by exposing dimethylsilyl cyclohexadiene        cis-diol acetonide (4b) to hydrogen gas or diimide.

In accordance with another aspect of the present invention, cis-diolsand acetonides having a hydrosilane function may be derivatized byreacting the hydrosilane function. For example, the cis-diol oracetonide may have formulas of:

wherein:

-   -   R¹ and R² are each independently selected from hydrogen, a        halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or        branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl,        halomethyl, OR, SR, NR₂₋₃, or O(CO)R;    -   R⁴ is selected from hydrogen, a halogen, linear or branched        C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or        branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR,        NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene        or substituted arene moieties;    -   n is 0-3;    -   R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; and    -   X is nothing, a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈        alkenyl, and C₂-C₁₈ alkynyl spacer.

For example, the cis-diol or acetonide having a hydrosilane function mayby hydrolyzed to a corresponding silanol. For example, the cis-diol ofFormula (XIa) may be hydrolyzed to a silanol of the formula

wherein R¹, R², R⁴, X, and n are as defined above with respect toFormula (XIa). The acetonide of Formula (XIb) may be hydrolyzed to asilanol of the formula

wherein R¹, R², R⁴, X, and n are as defined above with respect toFormula (XIb). For example, the silanol may be

which may be made by reacting dimethylsilyl cyclohexadiene cis-diol (2b)with NaOH, ACN/H₂0. The silanol may be further condensed to form

In a further example, the silanol may be

which may be made by reacting dimethylsilyl cyclohexadiene cis-diolacetonide (4b) with ACN and H₂0 at a pH of greater than about 9. Thesilanol may be further condensed to form

In another example, the cis-diol or acetonide having a hydrosilanefunction may be subject to alcoholysis to form an alkoxy derivative. Forexample, the cis-diol of Formula (XIa) or the acetonide of Formula (XIb)may be subject to alcoholysis to form a alkoxy derivatives of theformulas

wherein R¹, R², R⁴, X, and n are as defined above with respect toFormulae (XIa, XIb), and R⁵ is an aryl, a linear or branched C₁-C₁₈alkyl, a linear or branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈alkynyl. For example, the alkoxy derivative may be

which may be made by reacting dimethylsilyl cyclohexadiene cis-diolacetonide with ethyl alcohol and sodium metal. In a further example, thealkoxy derivative may be

which may be made by reacting dimethylsilyl cyclohexadiene cis-diolacetonide with isopropyl alcohol and Pt(IV).

In a further example, the cis-diol or acetonide bearing eitherhydrosilane or vinylsilane functionality are subjected tohydrosilylation reactions resulting in the formation of a silicon-carbonbond.

Scheme 5 shown below illustrates a number of the reactions ofdimethylsilyl cyclohexadiene cis-diol (2b) as discussed above.

Scheme 6 shown below illustrates a number of the reactions ofdimethylsilyl cyclohexadiene cis-diol acetonide (3b) discussed above.

In order that the invention may be more readily understood, reference ismade to the following examples, which are intended to be illustrative ofthe invention, but are not intended to be limiting in scope.

EXAMPLE 1

Conversion of the six aryl silanes illustrated in Scheme 1 to thecorresponding cis-diols was done using E. coli strain JM109 (pDTG601)expressing the P. putida F1 toluene dioxygenase genes (todC1C2BA) (SEQID No. 1). Cells were grown in minimal salts broth (MSB) in either ashake flask or 14 L fermentor and harvested upon attaining OD 70(Hudlicky, T. et al. (1999) Organic Syntheses, Vol. 76, 77). The cellmass was resuspended in 100 mM phosphate buffer having a pH of 7.4 andcontaining 5 g/L glucose to OD 35. Aryl silane substrates (1-20 g/L)were added and the mixtures were incubated at 37° C. at 225 rpm for 6hours. The pH of the mixture was adjusted back up to pH 7.4 after aninitial 2 hour incubation.

The whole broth was then centrifuged to remove the cells and thesupernatant separated and extracted with ethyl acetate followingsaturation with sodium chloride. The organic extract was dried oversodium sulfate, filtered and concentrated under vacuum. The remainingmaterial was subjected to 300 MHz NMR and GC/MS analysis to determinethe extent of conversion to the cis-diol products. The products areillustrated above in Scheme 1.

The products were analyzed. Dimethylphenylvinylsilane cis-diol (2a)[(1S, 2S)-3-(dimethylvinylsilyl)cyclohexa-3,5-diene-1,2-diol] ¹H NMR(300 MHz, d₆-DMSO) δ 6.21, dd, J=24.5, 14.4 Hz, H3′; 6.11, dt, J=1.6,6.3 Hz H4; 5.96, dd, J=14.4, 4.1 Hz, H2′; 5.90, ddd, H5; 5.80, ddd, H6;5.71, dd, J=24.5, 4.1 Hz, H1′; 4.02, m, H2; 3.96, m, H1; 0.18, s, 6H,SiMe. GC/MS: 178 [M-18]⁺.

Dimethylphenylsilane cis-diol (2b) [[(1S,2S)-3-(dimethylsilyl)cyclohexa-3,5-diene-1,2-diol] ¹H NMR (300 MHz,d₆-DMSO) δ 6.27, dt, J=1.5, 6.3 Hz H4; 5.98, dd, J=14.4, 4.1 Hz, H5;5.95, ddd, H6; 4.20, dd, J=10.5, 2.2 Hz, H1; 4.17, sept, J=6.0 Hz, SiH;4.07, bdd, J=10.5, 6.0 Hz, H2; 0.21, d, 6H, SiMe. GC/MS: 152 [M-18]⁺.

Phenyltrimethylsilane cis-diol (2c) [[(1S,2S)-3-(trimethylsilyl)cyclohexa-3,5-diene-1,2-diol] ¹H NMR (300 MHz,d₆-DMSO) δ 6.21, dt, J=5.0, 1.0 Hz H4; 5.97, ddd, J=9.5, 6.3, 1.4 Hz,H5; 5.88, dddd, H6; 4.06, m, 2H, H1, 2; 0.05, d, 6H, SiMe. GC/MS: 166[M-18]⁺.

Benzyltrimethylsilane cis-diol (2d) [[(1S,2S)-3-(trimethylsilylmethyl)cyclohexa-3,5-diene-1,2-diol] ¹H NMR (300MHz, d₆-DMSO) δ 5.87, ddd, J=9.5, 5.3, 2.1 Hz, H5; 5.61, bdd, J=3.1 Hz,H6; 5.55, bdd, H4; 4.21, m, H1; 3.78, d, J=6.0 Hz, H2; 1.78, 1.68, 2d,J=13.6 Hz, SiCH₂; 0.04, s, 9H, SiMe. GC/MS: 180 [M-18]⁺.

Methylphenylvinylsilane cis-diol (2e) [[(1S,2S)-3-(methylvinylsilyl)cyclohexa-3,5-diene-1,2-diol] ¹H NMR (300 MHz,d₆-DMSO) δ 6.27, m, (R,S)—H4; 6.21, 6.20, 2dd, J=20.1, 14.6 Hz,(R,S)—H3′; 6.08, 6.06, 2dd, J=14.6, 4.7 Hz; 6.03, m, 2H, (R,S)—H5,6;5.85, 5.84, 2dd, J=20.1, 4.5 Hz, (R,S)—H1′; 4.35, m, 2H, (R,S)—H2, SiH;4.15, m, (R,S)—H1; 0.32, 0.31, 2d, J=3.6 Hz, SiMe. GC/MS: 164 [M-18]⁺.

(Chloromethyl)dimethylphenylsilane cis-diol (2f) GC/MS: 166 [M-18]⁺.

EXAMPLE 2

The bioconversion of cis-diols was performed in a shake flask. Cells fortransformation in shake flask were grown either in separate shake flaskculture or in a 14 L fermentor (see Example 3). For the shake flask, 0.5L MSB media with ampicillin (100 μg/mL) in a 2.8 L baffled Fernbachflask was inoculated with 1 mL of a fresh seed culture of JM109(pDTG601) or JM109 (pDTG602) placed in a orbital shaker/incubator (250rpm, 37° C.). After 4-6 hours the cells were induced with IPTG (10 mg/L)and incubated an additional 6-8 hours until OD₆₀₀=1.0. For the 14 Lfermentor method, cells were harvested at OD₆₀₀=30-60. Cells werecollected by centrifugation and resuspended in transformation buffer(200 mM phosphate buffer pH 7.0, 0.4% glucose) to OD₆₀₀=10.Tranformations were done in a baffled Erlenmeyer flask equipped with avapor bulb (Hudlicky, T. et al. Organic Syntheses, Vol. 76, 77), withthe substrates (0.8-8 mg/mL) being added directly to the broth or to thevapor bulb and contacted with the cells for 34 hours (300 rpm, 37° C.).The products were extracted from the whole broth with dichloromethane.The organic extract was dried over sodium sulfate, filtered andconcentrated to give the cis-diol products as oils.

EXAMPLE 3

A scaled-up conversion of dimethylphenylvinylsilane to the correspondingcis-diol in a14 fermentor was performed. Dimethylphenylvinylsilane (1a)(25 g, 0.15 mol) was contacted with cells of an E coli. strainexpressing the dioxygenase JM109(pDTG601) that had been grown in a 14 Lstirred fermentor at pH 7.0 and 37° C. to an OD of over 20. The silanewas introduced into the fermentor at a rate such as to not adverselyalter the viability of the bacterial cells, typically at or below 1mL/min. The extent of conversion was followed by ¹H NMR and GC/MSanalysis of samples drawn from the fermentor until nodimethylphenylvinylsilane was detected. At that point the broth wascollected and the cells removed by centrifugation. The supernatant waspassed through a 10K cutoff size exclusion filter and extracted threetimes with ethyl acetate (1 L). The combined organic extracts were driedover sodium sulfate, filtered and the solvent removed under reducedpressure to give the corresponding cis-diol (2a) as a dark oil (12 g,40%).

In a similar manner to that described above dimethylphenylsilane (1b)(50 g, 0.37 mol) was converted to the cis-diol (2b) as a tan oil thatslowly crystallized in the refrigerator (36 g, 64%).

In a similar manner to that described above benzyltrimethylsilane (1d)(25 g, 0.15 mol) was converted to the cis-diol (2d) (8 g, 22%).

The enantiomeric excess (% ee) and absolute configuration of purifieddiols cis-(1S,2S)-3-(dimethylvinylsilyl)cyclohexa-3,5-diene-1,2-diol(2a) and cis-(1S,2S)-3-(dimethylsilyl)cyclohexa-3,5-diene-1,2-diol (2b)is greater than 98% ee as determined by the ¹H NMR method of Resnick etal. (Resnick, S. M.; Torok, D. S.; Gibson, D. T. J. Am. Chem. Soc. 1995,60, 3546-3549).

EXAMPLE 4

The cis-diols (2a-e) were converted to acetonide derivatives (3a-e) asshown in Scheme 2. The cis-diols were converted to the more stableacetonide derivatives by treatment of a solution of the diol in2,2-dimethoxypropane with a trace of Amberlite 118-H⁺ acid resin overseveral hours. Filtration of the reaction mixture was followed byevaporation of the solvent. The crude acetonides were purified on asilica gel column by elution with ethyl acetate/hexane (1:9). Analysisof the ¹H and ¹³C NMR spectra confirmed the identity of the compounds.

Dimethylphenylvinylsilane cis-diol acetonide (3a)[cis-4-(dimethylvinylsilyl)-2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxazole]¹H NMR (300 MHz, CDCl₃) δ 6.21, dd, J=19.8, 14.7 Hz, H3′; 6.21, dt,J=5.3, 0.9 Hz, H5; 6.01, dd, J=14.7, 4.1 Hz, H2′; 5.99, ddd, J=9.3, 5.3,1.0 Hz, H6; 5.87, ddd, J=9.3, 3.6, 1.0 Hz, H7; 5.74, dd, J=19.8, 4.4 Hz,H1′; 4.74, dd, J=9.0, 0.9 Hz, H3a; 4.59, ddd, J=9.0, 3.6, 1.0 Hz, H7a;1.35, 1.31, 2s, 6H, 0.18, 2s, 6H, SiMe.

Dimethylphenylsilane cis-diol acetonide (3b)[cis-4-(dimethylsilyl)-2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxazole] ¹HNMR (300 MHz, CDCl₃) δ 6.23, bd, J=5.6 Hz, H5; 6.01, dd, J=9.8, 5.6 Hz,H6; 5.94, dd, J=9.8, 1.2 Hz, H7; 4.72, bd, J=9.0 Hz, H3a; 4.54, dd,J=9.0, 4.0 Hz, H7a; 4.12, sept, J=4.0 Hz, SiH; 1.37, 1.35, 2s, 6H, 0.21,2d, 6H, SiMe.

Phenyltrimethylsilane cis-diol acetonide (3c)[cis-4-(trimethylsilyl)-2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxazole]¹H NMR (300 MHz, CDCl₃) δ6.20, dt, J=5.6, 0.9 Hz, H5; 6.01, ddd, J=9.9,5.4, 0.9 Hz, H6; 5.86, ddd, J=9.9, 3.8, 1.0 Hz, H7; 4.74, dd, J=9.0, 0.8Hz, H3a; 4.59, ddd, J=9.0, 3.6, 0.8 Hz, H7a; 1.31, 1.36, 2d, 6H, 0.13,s, 9H, SiMe.

Methylphenylvinylsilane cis-diol acetonide (4d)[cis-4-[(R,S)-methylvinylsilyl]-2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxazole]¹H NMR (300 MHz, CDCl₃) δ6.28, 6.25, 2bd, (R,S)—H5; 6.20, 6.19, 2ddd,J=19.1, 14.3, 1.7 Hz, (R,S)—H3′; 6.07, 6.05, 2dd, J=14.3, 4.3 Hz,(R,S)—H2′; 6.02, bdd, 9.6, 4.8 Hz, (R,S)—H6; 5.95, bddd, J=9.6, 3.9, 1.3Hz, (R,S)—H7; 5.86, 5.85, 2ddd, J=19.6, 4.3, 3.6 Hz, (R,S)—H1′; 4.72,bdt, J=8.4, 1.1 Hz, (R,S)—H3a; 4.53, 4.52, 2dd, J=8.4, 2.1 Hz,(R,S)—H7a; 4.30, bdq, J=3.6 Hz, SiH; 1.38, 1.36, 2bs, 6H, 0.31, 2d,J=3.7 Hz, SiMe.

EXAMPLE 5

The conversion of cis-diols to catechol derivatives was performed.Conversion of cis-diols to the corresponding catechols was effectedusing E. coli strain JM109 (pDTG602) expressing the(+)-cis-(1S,2R)-dihydroxy-3-methylcyclohexa-3,5-diene dehydrogenase gene(todD) from Pseudomonas putida F1. Transformations were conducted in ashake flask as described in Example 2. Dimethylphenylvinylsilanecis-diol (2a) or dimethylphenylsilane cis-diol (2b) was added directlyto the re-suspended cells (1-2 mg diol/mL transformation broth) andincubated for 34 hours. The whole broth was extracted with ethyl acetatefor analysis of the products. TLC: extracts of both transformations(silica gel, chloroform:acetone, 4:1) showed two UV-active bands atR_(f)≈0.4 and 0.6, the latter turning dark brown immediately aftertreatment with Gibbs reagent (0.1% 2,6-dichloroquinone chlorimide inethanol). GC/MS: 1-dimethylvinylsilyl-2,3-benezene diol (4a): m/z (rel.intensity) 194 (M⁺, 4%), 166 (100%); 1-dimethylsilyl-2,3-benzene diol(4b): m/z (rel. intensity) 168 (M⁺, 42%), 153 (96%), 75 (100%).

EXAMPLE 6

Cycloadducts (5a, b) of silane cis-diol acetonides as shown in Scheme 4were produced. The dimethylphenylvinylsilyl cis-diol acetonide (3a) wasfound to form a novel product when left to stand at room temperature inconcentrated form over the course of a week or more. Purification of thematerial by column chromatography on silica gel gave the cycloadduct(5a) as a colorless oil. ¹H NMR (300 MHz, CDCl₃) δ6.30, 6.18, 2dd, J=20,14.4 Hz, 2H, 5.86-6.10, m, 5H, 7.72, 5.65, 2dd, J=20, 3.8 Hz, 2H,4.18-4.28, m, 3H, 4.01, dd, J=5.2, 3.4 Hz, 1H, 2.90, m, H4; 2.38, bdd,J=8.7, 3.2 Hz, H4′; 2.05, bd, H5′; 1.32, 1.30, 1.23, 1.21, 4s, 12H,0.24, 0.22, 0.16, 0.15, 4s, 12H, SiMe.

In the same manner as described above dimethylsilyl cis-diol acetonide(3b) was converted into the cycloadduct (5b). The material was purifiedas previously described to give a colorless oil. ¹H NMR (300 MHz,CDCl₃); δ 6.10, dd, J=4.0, 1.4 Hz, H4′; 6.04, bt, J=8 Hz, H5; 5.83, d,J=8 Hz, H4; 4.10-4.30, m, 4H, H1,2, 1′,2′; 4.09, septuplet, 2H, J=3.8Hz, SiH; 2.86, m, H6; 2.36, dd, J=9.0, 3.8 Hz, H5′; 2.18, bd, J=9.0 Hz,H6′; 1.25, 1.22, 1.21, 12H, 0.22, 0.21, 0.17, 3d, 12H, SiMe. GC/MS;

EXAMPLE 7

Epoxy derivatives of the dimethylsilyl cis-diol acetonide (3b) as shownin Scheme 6 were produced. A solution of the acetonide (3b) (90 mg, 0.43mmol) in dichloromethane (4 mL) was contacted with 2 mol equivalents ofm-chloroperbenzoic acid (m-CPBA) at −10° C. After disappearance of thestarting material (TLC), the reaction was extracted with saturatedNaHCO₃ and the organic extract concentrated to give an oil. Purificationon silica gel (hexane to hexane/EtOAc 2:1) gave a first a pair of epoxyhydrosilanes (6a, 7a, 2:1)(20 mg, 20%) followed by a pair of epoxysilanols (6b, 7b, 2:1)(41 mg, 39%). The 1,6-epoxy regioisomers were themajor products. ¹H NMR (300 MHz) 6a: δ6.05, ddd, J=10.3, 6.2, 1.7 Hz,H5; 5.76, dm, J=10.3 Hz; H6; 4.70, bd, J=6.0 Hz, H2; 4.36, dt, J=7.2,2.4 Hz, H1; 4.01, sept, J=3.9 Hz, SiH; 3.16, dt, J=6.6, 1.2 Hz, H4;1.36, 2s, 6H; 0.2, 2s, 6H, SiMe. 6b: δ6.05, ddd, J=10.3, 6.2, 1.7 Hz,H5; 5.77, dm, J=10.3 Hz; H6; 4.76, bd, J=7.0 Hz, H2; 4.37, dt, J=7.2,2.4 Hz, H1; 3.25, dt, J=6.6, 1.2 Hz, H4; 2.4-2.8, b, 1H, SiOH; 1.36, 2s,6H, 0.28, 0.22, 2s, 6H, SiMe. 7a: δ6.31, dd, J=5.4, 1.7 Hz, H4; 4.73,dd, J=7.2, 2.4 Hz, H2; 4.54, dd, J=7.2, 1.8 Hz, H1; 4.11, sept, J=3.9Hz, SiH; 3.55, dd, J=5.4, 1.9 Hz, H6; 3.29, td, J=5.4, 1.2 Hz, H5; 1.38,s, 6H; 0.2, 2s, 6H, SiMe. 7b: δ6.31, dd, J=5.4, 1.7 Hz, H4; 4.76, d,J=7.0 Hz, H2; 4.63, dd, J=7.0, 1.9 Hz, H1; 3.54, dd, J=5.4, 1.9 Hz, H6;3.29, td, J=5.4, 1.2 Hz, H5; 2.4-2.8, b, 1H, SiOH; 1.39, 2s, 6H, 0.22,0.21, 2s, 6H, SiMe.

EXAMPLE 8

The dimethylsilyl cis-diol acetonide (3b) was reacted with sodiumethoxide. Freshly cut sodium (113 mg, 4.9 mmol) was added to anhydrousethanol (freshly distilled from Mg) under an inert atmosphere. After allreaction had ceased, the solution was cooled in an ice/salt bath and theacetonide (3b) (155 mg, 0.74 mmol) was added. TLC soon after additionshowed no starting material and a major product (R_(f) 0.57, silica gel,hexanes:MTBE, 2:1, visualization: KMnO₄). The reaction was quenched withacetic acid (5.1 mmol), allowed to come to ambient temperature, dilutedwith dichloromethane, filtered and evaporated. ¹H-NMR showed a compoundidentified as the ethoxysilane (8) as shown below. ¹H NMR (300 MHz) δ6.18, d, 1H, 5.9, m, 1H, 5.7, m, 1H; 4.7, d, 1H; 4.55, d, 1H, 1.6, m;0.02, d, 6H.

EXAMPLE 9

The dimethylsilyl cis-diol acetonide (3b) was reacted with isopropanol.A solution of the cis-diol acetonide (3b) (100 mg, 0.48 mmol) inisopropanol (3 mL) was treated with chloroplatinic acid (H₂PtCl₄, 0.005mol %) at 50° C. over 24 h. TLC indicated the disappearance of thestarting material and the formation of a new product. The reactionmixture was concentrated and purified on silica gel (ethylacetate/hexane, 1:10) to give the isopropoxysilane (9) as a colorlessoil. ¹H NMR (300 MHz, CDCl₃) δ6.32, bd, J=5.4 Hz, H5; 6.00, ddd, J=9.6,5.4, 1.2 Hz, H6; 5.90, ddd, J=9.8, 3.6, 1.2 Hz, H7; 4.70, dd, J=8.8, 1.0Hz, H3a; 4.59, ddd, J=8.8, 3.8, 1.2 Hz, H7a; 4.03, sept, J=6.2 Hz,Me₂CH; 1.37, 1.36, 2s, 6H, 1.14, 1.15, 2d, J=6.2 Hz, Me₂CH; 0.26, 0.24,2s, 6H, SiMe.

EXAMPLE 10

The hydrogenation of the dimethylsilyl cis-diol acetonide (3b) wasperformed. The acetonide (3b) (130 mg, 0.7 mmol) was dissolved in MTBEin a test tube. 5% rhodium on alumina (30 mg) was added and the mixturewas hydrogenated on a Parr-shaker at 65 psi under hydrogen gas (H₂) for24 hrs. The mixture was filtered through celite and dried under reducedpressure. Solvent exchange using 3 dissolution/dry-down cycles withdeuterochloroform successfully purged the product of MTBE. Analysis by¹H-NMR showed mostly the completely saturated analogue. Decouplingexperiments demonstrated that the hydrosilane functionality was intact.GC/MS showed that the major component was the hexahydroaromatic: m+/e199 (—CH₃), and 156 (—C₃H₆O). The products shown below were present.

EXAMPLE 11

The conversion of a cis-diol acetonide to the silanol (11) wasperformed. A solution of the acetonide (3b) (90 mg, 0.43 mmol) inDCM/ACN (4 mL, 1:1) was contacted with a 1N NaOH solution (4 mL) withstirring over 2 h. TLC indicated the consumption of the startingmaterial and the appearance of two new compounds. The reaction mixturewas diluted with DCM (10 mL) and the organic layer isolated and washedwith water and saturated brine solution. The organic extract was thendried over sodium sulfate, filtered and concentrated to give a mixtureof the silanol (11 a) and the disiloxane (11b) as an oil (65 mg, 4:1).¹H NMR (300 MHz, CDCl₃) 11a: □6.23, dt, 1H, 6.04, dd, 1H, 5.95, ddd, 1H,4.83, dd, 1H, 4.56, dd, 1H, 2.50, bs, 1H, 1.36, s, 6H, 0.26, 0.25, 2s,6H. 11b: □6.26, dm, 1H, 5.97, m, 1H, 5.88, ddd, 1H, 4.71, dd, 1H, 4.56,m, 1H, 1.35, 2s, 6H, 0.22, s, 6H.

EXAMPLE 12

The hydrosilylation of cis-diol acetonides may be performed. Thecis-diol acetonides of this invention bearing either hydrosilane orvinylsilane functionality may be subjected to hydrosilylation reactionsresulting in the formation of a silicon-carbon bond. For example theacetonide (3b) is contacted with an olefin and Wilkinsons catalyst[(Ph₃P)₃RhCl] in an appropriate solvent to yield a silane containing anadditional silicon-carbon bond.

EXAMPLE 13

The reduction of the dimethylsilyl cyclohexadiene cis-diol 2b withdiimide was performed. The diol (2b) was treated with diimide (N₂H₂)generated using freshly prepared potassium azodicarbonamide in aceticacid. Many products were observed on TLC. Column chromatography onsilica gel using ether in hexanes yielded a small amount of crystallinematerial that was impure by ¹H-NMR analysis. However, it appears thatthe major component was the1,2,3,4-tetrahydrocyclohex-5-ene-1,2-cis-diol (12). The silicon hydrideappears to have been hydrolyzed, presumably to either the silanol or thedisiloxane as shown below. ¹H NMR (300 MHz):

5.83-5.91, d of p, 1H, 5.5-5.56, d of m, 1H, 4.17, bs, 1H, 4.06, bs, 1H,3.92, sext., 1H.

EXAMPLE 14

The hydrogenation of the dimethylsilyl cyclohexadiene cis-diol (2b) wasperformed. The diol (180 mg, 1 mmol) was hydrogenated over 5% rhodium onalumina (35 mg). After 24 hours, the mixture was filtered through celiteand dried in vacuo. The ¹H NMR spectrum showed what appeared to be the1,2,5,6-tetrahydrocyclohex-3-ene (13a): 6.16 ppm, d of t. Some fullysaturated material (13b) must also be present judging from the signal at1.12 ppm, d of d, representing the methine hydrogen next to the silicon.Again, although more that 2 methyl signals are apparent, all are split,indicating that the hydrosilane groups are intact. The products areshown below.

EXAMPLE 15

The acetylation of the dimethylsilyl cyclohexadiene cis-diol wasperformed. The dimethylsilyl cis-diol (2b) (370 mg, 2.1 mmol) wastreated with pyridine (3 mL) and acetic anhydride (2 mL) at ice bathtemperature for 30 minutes, and then for a further 2 hours a roomtemperature. The reaction mixture was diluted with water (50 mL) andextracted with ethyl acetate (2×20 mL). The organic extract washedsequentially with saturated sodium bicarbonate solution and brine anddried over sodium sulfate. The extract was then filtered andconcentrated with the aid of toluene to remove traces of pyridine andacetic acid. The residue was purified on a silica gel column(EtOAc/hexane, 1:9 to 2:3) to give the diacetate (14) as an oil as shownbelow. ¹H NMR (300 MHz, d₆-DMSO): δ 6.42, dt, J=5.0, 1.5 Hz, H4; 6.22,ddd, J=9.2, 5.0, 1.2 Hz, H5; 6.01, ddd, J=9.2, 5.0, 1.2 Hz, H6; 5.56,dd, J=5.8, 2.3 Hz, H2; 5.36, ddd, J=5.8, 5.0, 1.2 Hz, H1; 4.36, sept,J=3.8 Hz, SiH; 2.01, 1.96, 2s, 6H, Ac; 0.29, d, 6H, SiMe.

EXAMPLE 16

The dimethylsilyl cyclohexadiene cis-diol was converted to the silanol(15). A solution of the dimethylsilyl cis-diol (2b) (500 mg, 2.9 mmol)in a mixture of acetonitrile/water (5 mL, 4:1) was treated with 1Nsodium hydroxide (300 μL) at room temperature. A gas was immediatelyseen to form and TLC indicated the formation of a new lower Rf compound.Reverse phase chromatography on C18 silica gave the silanol (15) as atan colored oil as shown below. ¹H NMR (300 MHz, d₆-DMSO) δ 6.18, m, H4;5.90, m, H5; 5.86, m, H6; 4.05, m, H2; 3.95, m, H1; 0.18, s, 6H, SiMe.

EXAMPLE 17

The silane cis-diols of this invention were converted to the meta-and/or ortho-phenols through contacting the cis-diols with acid in wateror water/solvent mixtures. The phenolic products were readily detectedon TLC with Gibb's reagent.

EXAMPLE 18

The hydrosilylation of hydro- and vinyl silane cis-diols may beperformed. The cis-diols of this invention bearing either hydrosilane orvinylsilane functionality may be subjected to hydrosilylation reactionsresulting in the formation of a silicon-carbon bond. For example theacetonide (2b) is contacted with an olefin and Wilkinsons catalyst[(Ph₃P)₃RhCl] in an appropriate solvent to yield a silane containing anadditional silicon-carbon bond.

It will be obvious to those skilled in the art that various changes maybe made without departing from the scope of the invention, which is notto be considered limited to what is described in the specification.

1. A compound comprising an acetonide having the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, a halogen, an aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, OR, SR, NR₂₋₃, or O(CO)R, except when R¹═R²═R³ then R¹═R²═R³ cannot be —CH₃; and R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³.
 2. The compound as claimed in claim 1 wherein: R¹, R², and R³ are each independently selected from hydrogen, a linear or branched C₁-C₅ alkyl, a linear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl, halomethyl, or OR; and R is hydrogen, methyl, or ethyl.
 3. The compound as claimed in claim 1 wherein R¹, R², and R³ are each independently selected from hydrogen, methyl, chloromethyl, or vinyl.
 4. The compound as claimed in claim 1 wherein said acetonide comprises:


5. The compound as claimed in claim 1 wherein said acetonide comprises:


6. The compound as claimed in claim 1 wherein said acetonide comprises:


7. A compound comprising an acetonide having the formula:

wherein: R¹, R², and R³ are each independently selected from hydrogen, a halogen, aryl, a linear or branched C₁-C₁₈ alkyl, a linear or branched C₂-C₁₈ alkenyl, a linear or branched C₂-C₁₈ alkynyl, halomethyl, OR, SR, NR₂₋₃, or O(CO)R; R⁴ is selected from hydrogen, a halogen, linear or branched C₁-C₁₈ alkyl, linear or branched C₂-C₁₈ alkenyl, linear or branched C₂-C₁₈ alkynyl, halomethyl, CF₃, CN, NO₂, SR, OR, NR₂₋₃, O(CO)R, SiR¹R²R³, or a bridging group between two arene or substituted arene moieties; n is 0-3; R is hydrogen, linear or branched C₁-C₁₈ alkyl, or SiR¹R²R³; X is a divalent linear or branched C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, or C₂-C₁₈ alkynyl spacer, except when X═C₂ alkynyl and R¹═R²═R³ then R¹═R²═R³ cannot be —CH₃.
 8. The compound as claimed in claim 7 wherein: R¹, R², and R³ are each independently selected from hydrogen, a linear or branched C₁-C₅ alkyl, a linear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl, halomethyl, or OR; R⁴ is selected from hydrogen, halogen, a linear or branched C₁-C₅ alkyl, a linear or branched C₂-C₅ alkenyl, a linear or branched C₂-C₅ alkynyl, CN, NO₂, OR or SiR¹R²R³; R is hydrogen, methyl, or ethyl; and X is either a divalent linear or branched C₁-C₅ alkyl, C₂-C₅ alkenyl, or C₂-C₅ alkynyl spacer.
 9. The compound as claimed in claim 7 wherein: R¹, R², and R³ are each independently selected from hydrogen, methyl, chloromethyl, or vinyl; R⁴ is selected from hydrogen, halogen, a linear or branched C₁-C₃ alkyl, a linear or branched C₂-C₃ alkenyl, a linear or branched C₂-C₃ alkynyl, CN, NO₂, OR or SiR¹R²R³.
 10. The compound as claimed in claim 7 wherein said acetonide comprises: 